POS0235 INTEGRATED SAFETY ANALYSIS UPDATE FOR FILGOTINIB (FIL) IN PATIENTS (PTS) WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS (RA) RECEIVING TREATMENT OVER A MEDIAN OF 2.2 YEARS (Y)
Authors: K. Winthrop, Y. Tanaka, T. Takeuchi, A. Kivitz, M. C. Genovese, A. Pechonkina, F. Matzkies, B. Bartok, K. Chen, D. Jiang, I. Tiamiyu, R. Besuyen, S. Strengholt, G. R. Burmester, J. E. Gottenberg
Journal: Annals of the Rheumatic Diseases (2022)

Background The preferential Janus kinase-1 inhibitor FIL significantly improved signs and symptoms of RA in Phase 2 and 3 trials. 1–5 FIL is approved for treatment of moderate to severe active RA in Europe and Japan. Integrated safety analysis of FIL with patient data through 2019 was presented at the 2020 ACR virtual meeting. 6 Objectives To report updated, as-treated data from the FIL integrated safety analysis with increased study drug exposure. Methods Data were integrated from 2 Phase 2 ( NCT01668641 , NCT01894516 ), 3 Phase 3 ( NCT02889796 , NCT02873936 , NCT02886728 ), and 2 long-term extension (LTE) ( NCT02065700 , NCT03025308 ) trials. Phase 2 and 3 LTE data were through Nov 2020 and Jan 2021, respectively. The as-treated analysis set included all available data for pts receiving ≥1 dose FIL 200 (FIL200) or 100 mg (FIL100), including those rerandomized to FIL for LTE. Exposure-adjusted incidence rates (EAIR)/100 patient-y exposure (PYE) of treatment-emergent adverse events (TEAEs; onset after first dose and no later than 30 days after last dose or new drug first dose date −1 day) and TEAEs of special interest (AESIs) are presented. Results 3691 pts received FIL200 or FIL100 for 8085.1 PYE (median 2.2, maximum 6.8 y). In the as-treated set, 61% of FIL200 and 45% of FIL100 pts received FIL for ≥2 y, 19% and 5% for ≥3 y, and 11% and 0.5% for ≥4.5 y, respectively. EAIR for TEAEs was higher with FIL100 than FIL200; EAIRs for deaths were 0.5 and 0.3 for FIL200 and FIL100 (Figure 1). Incidences of infections and serious infections were numerically greater for FIL100 vs FIL200, while EAIRs for other AESIs were comparable between doses (Table 1). EAIRs for AESIs tended to decrease since the previous update, except for venous thromboembolism (total FIL 0.1 to 0.2) and malignancies excluding NMSC (total FIL 0.5 to 0.6). Table 1. TEAEs of special interest, as-treated set TEAE, n (%) and EAIR per 100 PYE (95% CI) FIL 200 mgn=2267PYE=5302.5 FIL 100 mgn=1647PYE=2782.6 Total FILN=3691PYE=8085.1 Infectious AEs 1206 (53.2) 747 (45.4) 1927 (52.2) EAIR 21.1 (19.7, 22.5) 30.2 (26.8, 34.0) 21.0 (19.9, 22.3) Serious infectious AEs 80 (3.5) 57 (3.5) 137 (3.7) EAIR 1.5 (1.1, 1.9) 2.7 (1.9, 3.9) 1.6 (1.3, 2.0) Opportunistic infections 5 (0.2) 4 (0.2) 9 (0.2) EAIR 0.1 (0, 0.2)* 0.1 (0.1, 0.4)* 0.1 (0.1, 0.2)* Active tuberculosis 0 3 (0.2) 3 (&lt;0.1) EAIR 0 0.1 (0, 0.3)* 0 (0, 0.1)* Herpes zoster 84 (3.7) 30 (1.8) 114 (3.1) EAIR 1.6 (1.2, 2.0) 1.1 (0.8, 1.5)* 1.4 (1.1, 1.7) Major adverse cardiovascular events a 19 (0.8) 14 (0.9) 33 (0.9) EAIR 0.3 (0.2, 0.5) 0.5 (0.3, 0.8)* 0.4 (0.2, 0.6) Venous thromboembolism b 11 (0.5) 4 (0.2) 15 (0.4) EAIR 0.2 (0.1, 0.4)* 0.1 (0.1, 0.4)* 0.2 (0.1, 0.3)* Atrial systemic thrombotic events a 1 (&lt;0.1) 1 (&lt;0.1) 2 (&lt;0.1) EAIR 0 (0, 0.1) 0 (0, 0.3) 0 (0, 0.1) Malignancy excluding NMSC 32 (1.4) 17 (1.0) 49 (1.3) EAIR 0.6 (0.4, 0.9) 0.6 (0.4, 1.0)* 0.6 (0.4, 0.8) NMSC 15 (0.7) 5 (0.3) 20 (0.5) EAIR 0.3 (0.2, 0.5)* 0.2 (0.1, 0.4)* 0.2 (0.2, 0.4)* Gastrointestinal perforations 3 (0.1) 1 (&lt;0.1) 4 (0.1) EAIR 0.1 (0, 0.2)* 0 (0, 0.3)* 0 (0, 0.1)* *Except when any study had 0 event within the treatment, the Poisson model was not adjusted by study. PYE was defined as (last dose date − first dose date + 1)/365.25. a Positively adjudicated. b Adjudicated as deep vein thrombosis or pulmonary embolism. NMSC, nonmelanoma skin cancer Conclusion With 1 additional year of exposure since the 2020 report, FIL continues to be well tolerated with no new safety concerns emerging. EAIRs of TEAEs, including deaths, and AESIs remained stable or decreased since the 2020 report, except for slight increases in rates of NMSC and malignancies excluding NMSC. In the context of demonstrated efficacy, both FIL doses had an acceptable risk/benefit profile. References [1]Westhovens R et al. Ann Rheum Dis 2017;76:998–1008. [2]Kavanaugh A et al. Ann Rheum Dis 2017;76:1009–19. [3]Combe B et al. Ann Rheum Dis 2021;80:848–58. [4]Genovese MC et al. JAMA 2019;322:315–25. [5]Westhovens R et al. Ann Rheum Dis 2021;80:727–38. [6]Winthrop K et al. Arthritis Rheumatol 2020;72(suppl 10); abstract 0229. Acknowledgements Funding for DARWIN 1 and 2 was provided by Galapagos NV, and funding for DARWIN 3, FINCH 1, 2, 3, and 4 was provided by Gilead Sciences, Inc., Foster City, CA. Funding for this analysis was provided by Gilead Sciences, Inc. The sponsors participated in the planning, execution, and interpretation of the research. Medical writing support was provided by Gregory Bezkorovainy, MA, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA. Disclosure of Interests Kevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Gilead Sciences, Inc., GlaxoSmithKline, Pfizer, Roche, Regeneron, Sanofi, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, and Pfizer, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol Myers Squibb, Eisai, Chugai, AbbVie, Astellas, Pfizer, Sanofi, Asahi-Kasei, GSK, Mitsubishi-Tanabe, Gilead Sciences, Inc., and Janssen, Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Taisho, and Sanofi, Grant/research support from: AbbVie, Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, and Takeda, Tsutomu Takeuchi Speakers bureau: AbbVie, AYUMI, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly Japan, Gilead Sciences, Inc., Mitsubishi-Tanabe, Novartis, Pfizer Japan, and Sanofi, Consultant of: Astellas, Chugai, and Eli Lilly Japan, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan, Alan Kivitz Shareholder of: Amgen, Gilead Sciences, Inc., GlaxoSmithKline, Pfizer, and Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, and Sanofi, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, and Sanofi, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Genzyme, Gilead Sciences, Inc., Janssen, Novartis, Pfizer, Regeneron, Sanofi, and SUN Pharma Advanced Research, Mark C. Genovese Shareholder of: Gilead Sciences, Inc., Consultant of: AbbVie, Amgen, Beigene, Eli Lilly and Co., Genentech, Inc., Gilead Sciences, Inc., Sanofi Genzyme, RPharm, and SetPoint, Employee of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Kun Chen Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Iyabode Tiamiyu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos BV, Employee of: Galapagos BV, Sander Strengholt Shareholder of: Galapagos BV, Employee of: Galapagos BV, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., and Pfizer, Consultant of: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., and Pfizer, Jacques-Eric Gottenberg Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos BV, Gilead Sciences, Inc., Roche, Sanofi Genzyme, and UCB, Consultant of: Bristol Myers Squibb, Sanofi Genzyme, and UCB, Grant/research support from: Bristol Myers Squibb and Pfizer